Mice are useful for studying the role of genetics in taste sensation. There are numerous inbred mouse strains whose genotypes and ingestive behaviors have been characterized, and mice are used frequently for genetic manipulations. However, there have been no electrophysiological recordings from central gustatory areas in mice, and few studies in which taste-evoked activity was measured in single neurons, even though these procedures have proven useful in other species. In the proposed work, recordings will be made of taste-evoked activity of single neurons in the nucleus of the solitary tract (NST) of mice. Furthermore, mouse strains will be selected to allow for an investigation of individual genes thought to be involved in taste processing. In specific aim 1, NST responses will be measured to see whether they are affected by polymorphisms at the Sac locus, which is thought to code for a receptor involved in binding molecules labeled "sweet" by humans. Subjects will be C57BL/6ByJ (B6) and 129P3/J (129) mice, which differ on their preferences for "sweeteners," and congenic mice that contain one copy of the B6 Sac allele on a 129 background. In specific aim 2, NST activity will be measured to see whether it is affected by the absence of alpha-gustducin, a G-protein subunit though to be involved in transduction of "sweet" and "bitter" taste. Subjects will be mice with a null mutation in the alpha-gustducin gene ("knock-outs") and wild-type controls. The use of single-unit NST recording will allow for a thorough examination of how Sac and alpha-gustducin influence gustatory signals sent to the brain in mice, including how those signals are distributed to central neurons with different response profiles. The proposed studies will also contribute to understanding the mechanisms that underlie sweet and bitter taste sensation in humans. These sensations are known to influence dietary choices that affect the likelihood of specific health risks, such as cancer, and a more thorough understanding of sweet and bitter taste may lead to ways of modifying them to reduce the incidence of health problems.